Optimization and therapeutic effects of PDT mediated by ALA and MAL in the treatment of cutaneous malignant lesions: a comparative study

Abstract

5-aminolevulinic acid (ALA) and its methylated ester (MAL) are the most common topical agents used in photodynamic therapy (PDT) as precursors of the photosensitizer protoporphyrin IX (PpIX). The induction of newly PpIX depends on incubation time of each photosensitizer in the tissue and the presence of high intralesional porphyrin levels is an important parameter for the PDT effectiveness. This study used laser-induced fluorescence (LIF) spectroscopy to evaluate the optimum time to light exposure of PDT mediated by ALA (20% w/w) and MAL (10% w/w) to treat malignant lesions precursors of cutaneous squamous cell carcinoma induced in mice. The therapeutic effects obtained by optimized ALA- and MAL-PDT were assessed 10 and 20 days after treatments. Higher PpIX levels were evidenced in the lesions photosensitized by ALA than MAL and according to LIF measurements the PDT irradiation was performed, respectively, at 300 and 330 minutes after ALA and MAL incubation. Histopathological analysis evidenced necrosis and epithelial atrophy after 10 days of PDT using both prodrugs, as well as reepitelization and collagen deposition at 20 days. Thus, despite the distinct concentration of ALA and MAL used in the formulation of each photosensitizing cream, PDT mediated by both photosensitizing agents obtained similar therapeutic outcomes.